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Biomedical subjects

Elizabeth Murphy

Publications and source records attributed to Elizabeth Murphy.

47 records · Page 3Linked to original sources
PubMed2003

Medical emergencies at sea and injuries among Scottish fishermen.

BACKGROUND: It has long been known that fishing is one of the most dangerous occupations. In 2001, 33 boats were lost and 10 fishermen killed in UK waters. Despite the dangerous nature of the occupation, very little research has been conducted on fishermen's health and safety. Aims To address this gap in current knowledge, research was conducted to gain an understanding of health and lifestyle issues affecting Scottish fishermen. It was hoped that the study would identify aspects of fishermen's health that could be improved. This paper considers medical emergencies at sea and injuries among fishermen. METHODS: Data were collected using a postal questionnaire sent to the Scottish fishermen population and health diaries in a small sub-sample. RESULTS: In total, 1157 usable responses were received, giving a response rate of 57%. One-fifth of respondents had been involved in a medical emergency at sea that required them to be evacuated to shore for immediate treatment. The incidence of injuries was high, and one-third of the injuries experienced were to the back. The likelihood of evacuation for a medical emergency or experiencing an injury was increased both for certain occupations and with increasing number of boats worked on during the fisherman's career. CONCLUSION: Groups identified as being at a high risk of experiencing medical emergencies or injuries should be targeted in training initiatives or accident awareness and prevention initiatives.

Accidents, Occupational↗
PubMed2002

Ablation of PLB exacerbates ischemic injury to a lesser extent in female than male mice: protective role of NO.

Recent studies suggest a role for phospholamban phosphorylation during ischemia and reperfusion. The role of phospholamban in ischemia was studied by subjecting hearts from male and female wild-type (MWT/FWT) and phospholamban-knockout (MKO/FKO) mice to 20 min of ischemia-40 min of reperfusion while (31)P NMR spectra were acquired. ATP and pH values fell lower during ischemia, and postischemic contractility was less, in MKO and FKO versus WT hearts. After shorter ischemia (15 min), recoveries of contraction, ATP, and pH were greater in FKO than MKO hearts. To examine the role of nitric oxide (NO) synthases (NOS) in the protection in FKO versus MKO hearts, we utilized 1 microM l-NAME, a NOS inhibitor, or 100 microM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor. Recoveries of function, ATP, and pH were less in l-NAME-treated FKO than untreated FKO hearts and greater in SNAP-treated MKO than untreated MKO hearts. In conclusion, phospholamban ablation increased ischemic injury in both males and females; however, female hearts were less susceptible than male hearts. Protection in females was decreased by a NOS inhibitor and mimicked in males by an NO donor, implying that protection was NOS mediated.

Animals↗
PubMed2002

Alterations in apoptotic signaling in human idiopathic cardiomyopathic hearts in failure.

Dilated cardiomyopathy, a disease of unknown etiology and pathogenesis, is associated with heart failure and compensatory hypertrophy. Although cell and animal models suggest a role for altered gene expression in the transition to heart failure, there is a paucity of data derived from the study of human heart tissue. In this study, we used DNA microarray profiling to investigate changes in the expression of genes involved in apoptosis that occur in human idiopathic dilated cardiomyopathic hearts that had progressed to heart failure. We observed altered gene expression consistent with a proapoptotic shift in the TNF-alpha signaling pathway. Specifically, we found decreased expression of TNF-alpha- and NF-kappaB-induced antiapoptotic genes such as growth arrest and DNA damage-inducible (GADD)45beta, Flice inhibitory protein (FLIP), and TNF-induced protein 3 (A20). Consistent with a role for apoptosis in heart failure, we also observed a significant decrease in phosphorylation of BAD at Ser-112. This study identifies several pathways that are altered in human heart failure and provides new targets for therapy.

Adult↗
PubMed2002

Overexpression of A(3) adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts.

To determine whether A(3) adenosine receptor (A(3)AR) signaling modulates myocardial function, energetics, and cardioprotection, hearts from wild-type and A(3)AR-overexpressor mice were subjected to 20-min ischemia and 40-min reperfusion while (31)P NMR spectra were acquired. Basal heart rate and left ventricular developed pressure (LVDP) were lower in A(3)AR-overexpressor hearts than wild-type hearts. Ischemic ATP depletion was delayed and postischemic recoveries of contractile function, ATP, and phosphocreatine were greater in A(3)AR-hearts. To determine the role of depressed heart rate and to confirm A(3)AR-specific signaling, hearts were paced at 480 beats/min with or without 60 nmol/l MRS-1220 (A(3)AR-specific inhibitor) and then subjected to ischemia-reperfusion. LVDP was similar in paced A(3)AR-overexpressor and paced wild-type hearts. Differences in ischemic ATP depletion and postischemic contractile and energetic dysfunction remained in paced A(3)AR-overexpressor hearts versus paced wild-type hearts but were abolished by MRS-1220. In summary, A(3)AR overexpression decreased basal heart rate and contractility, preserved ischemic ATP, and decreased postischemic dysfunction. Pacing abolished the decreased contractility but not the ATP preservation or cardioprotection. Therefore, A(3)AR overexpression results in cardioprotection via a specific A(3)AR effect, possibly involving preservation of ATP during ischemia.

Adenosine Triphosphate↗
PubMed2002

Phosphorylation of glycogen synthase kinase-3beta during preconditioning through a phosphatidylinositol-3-kinase--dependent pathway is cardioprotective.

We previously reported that activation of phosphatidylinositol-3-kinase (PI3-kinase) is involved in ischemic preconditioning (PC). Our goal was to determine downstream targets of PI3-kinase. In perfused rat hearts, PC (4 cycles of 5 minutes of ischemia and 5 minutes of reflow) increased phosphorylation of glycogen synthase kinase-3beta (GSK-3beta), a downstream target of PI3-kinase and protein kinase B (PKB), an effect that was blocked by wortmannin. Because phosphorylation inactivates GSK-3beta, we examined whether PC-induced phosphorylation and inhibition of GSK-3beta is important in PC by using two inhibitors of GSK-3beta, lithium and SB 216763. Pretreatment of perfused rat hearts with lithium or SB 216763, before ischemia, mimicked the protective effects of PC; hearts treated with either lithium or SB 216763 had improved postischemic function and reduced infarct size. These findings indicate that inhibition of GSK-3beta is protective and that this PI3-kinase--dependent signaling pathway may play an important role in ischemic preconditioning.

Androstadienes↗
PubMed2002

Male and female mice overexpressing the beta(2)-adrenergic receptor exhibit differences in ischemia/reperfusion injury: role of nitric oxide.

OBJECTIVE: Cardiac overexpression of beta(2)-adrenergic receptors (beta(2)ARs) in male mice (MTG4) results in increased contractility and increased ischemic injury. Considering recent clinical data indicating that premenopausal women are protected from cardiovascular injury, we assessed the consequences of beta(2)AR overexpression in females (FTG4). Since protection in females is mediated via estrogen, which activates endothelial and inducible nitric oxide synthases (eNOS and iNOS) we also examined the role of NOS in ischemia/reperfusion injury in male and female TG4 and wild-type (WT) mice. METHODS: Hearts from MTG4, FTG4, MWT and FWT mice were isolated and perfused in the Langendorff mode. Hearts were pretreated with either 1 micromol/l of the nonspecific NOS inhibitor, L-NAME, or 100 nmol/l of the specific iNOS inhibitor, 1400W. Control hearts received no treatment. All hearts were subjected to 20 min ischemia and 40 min reperfusion while 31P-NMR spectra were acquired. RESULTS: During ischemia, ATP and pH fell lower in MTG4 hearts than in FTG4 or WT hearts. Hearts from MTG4 mice exhibited increased ischemia/reperfusion injury as indicated by lower recoveries of postischemic contractile function, ATP and PCr than WT. Despite contractility being elevated in FTG4 hearts to the same level as MTG4 hearts, ischemia/reperfusion injury was not increased, as indicated by similar postischemic recoveries of contractile function, ATP and PCr in FTG4 hearts compared to WT. ATP and pH fell lower during ischemia in L-NAME-treated FTG4 hearts than in untreated FTG4 hearts, falling as low as untreated MTG4s. Recoveries of contractile function, ATP and PCr were as low in L-NAME-treated FTG4 hearts as in untreated MTG4 hearts and lower than untreated FTG4 hearts. In contrast, 1400W had no effect on FTG4 hearts. MTG4 hearts were unaffected by L-NAME or 1400W. CONCLUSIONS: beta(2)AR overexpression increased ischemia/reperfusion injury in males but not females, thus females were protected from the detrimental effects of beta(2)AR overexpression. Protection was abolished by treatment with L-NAME, but not 1400W, implying that protection was mediated by eNOS not iNOS.

Amidines↗
PubMed2002

Expression of activated PKC epsilon (PKC epsilon) protects the ischemic heart, without attenuating ischemic H(+) production.

PKC epsilon is a PKC isoform that translocates during preconditioning and may mediate cardioprotection. To investigate whether PKC epsilon activation is cardioprotective, Langendorff-perfused hearts from wild-type (WT) mice and from mice expressing constitutively active mutant PKC epsilon were subjected to 20 min ischemia and 40 min reperfusion while(31)P NMR spectra were acquired. Pre-ischemic glycogen levels were similar in WT and PKC epsilon hearts. During ischemia, ATP fell less in PKC epsilon than in WT hearts. Ischemic intracellular pH, however, was similar in WT and PKC epsilon hearts. During reperfusion, recovery of contractile function and ATP were greater in PKC epsilon than WT hearts. In conclusion, expression of activated PKC epsilon protected hearts from post-ischemic energetic and contractile dysfunction, consistent with the proposed cardioprotective role of PKC epsilon. Protection occurred in the PKC epsilon hearts without attenuation of ischemic H(+) production, implying that, at least in this ischemic model, reduced acidification during ischemia is not necessary for cardioprotection.

Adenosine Triphosphate↗
PubMed2002

Is Na/Ca exchange during ischemia and reperfusion beneficial or detrimental?

Cytosolic calcium increases to approximately 3 micro M after 15 min of global ischemia. Manipulations that attenuate this increase in cytosolic Ca(2+) reduce myocyte death and dysfunction. The increase in cytosolic Ca(2+) during ischemia is dependent on an increase in intracellular Na(+), suggesting a role for Na/Ca exchange. Typical ischemic values for ionized intra- and extracellular Na(+), Ca(2+), and membrane potential are consistent with the Na/Ca exchanger operating near equilibrium during ischemia. Studies were undertaken using hearts from mice that overexpress the Na/Ca exchanger to determine if Na/Ca exchanger overexpression enhances or reduces ischemic injury. These studies suggest that overexpression of the Na/Ca exchanger enhances injury in males, but females are protected by a gender-related mechanism.

Animals↗
PubMed2002

Ca(2+) loading and adrenergic stimulation reveal male/female differences in susceptibility to ischemia-reperfusion injury.

To compare ischemia-reperfusion injury in males versus females under hypercontractile conditions, perfused hearts from 129J mice pretreated with 3 mmol/l Ca(2+) or 10(-8) mol/l isoproterenol +/- 10(-6) mol/l N(omega)-nitro-L-arginine methyl ester (L-NAME) were subjected to 20 min of ischemia and 40 min of reperfusion while (31)P NMR spectra were acquired. Basal contractility increased equivalently in female versus male hearts with isoproterenol- or Ca(2+) treatment. Injury was equivalent in untreated male versus female hearts but was greater in isoproterenol or Ca(2+)-treated male than female hearts, as indicated by lower postischemic contractile function, ATP, and PCr. Endothelial nitric oxide (NO) synthase (eNOS) expression was higher in female than male hearts, neuronal NOS (nNOS) did not differ, and inducible NOS (iNOS) was undetectable. Ischemic NO production was higher in female than male hearts, and L-NAME increased injury in female isoproterenol-treated hearts. In summary, isoproterenol or high Ca(2+) pretreatment increased ischemia-reperfusion injury in males more than females. eNOS expression and NO production were higher in female than male hearts, and L-NAME blocked female protection. Females were therefore protected from the detrimental effects of adrenergic stimulation and Ca(2+) loading via a NOS-mediated mechanism.

Adrenergic beta-Agonists↗
PubMedDate not supplied

S-nitrosylation: NO-related redox signaling to protect against oxidative stress.

Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a prevalent posttranslational protein modification involved in redox-based cellular signaling. Under physiologic conditions, protein S-nitrosylation and SNOs provide protection preventing further cellular oxidative and nitrosative stress. However, oxidative stress and the resultant dysfunction of NO signaling have been implicated in the pathogenesis of cardiovascular diseases.

Animals↗